期刊
JOURNAL OF CONTROLLED RELEASE
卷 258, 期 -, 页码 67-72出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.05.009
关键词
Ultrasound; Plasma membrane; Rupture; Sonodynamic therapy; Tumor ablation
资金
- NIH [GM094880]
The cell membrane is a semi-fluid container that defines the boundary of cells, and provides an enclosed environment for vital biological processes. A sound excitable drug (SED) that is non-cytotoxic to cells is developed to disrupt the plasma membrane under gentle ultrasound insonation, 1 MHz, 1 W/ cm2. The frequency and power density of insonation are within the physical therapy and medical imaging windows; thus the applied ultrasound is safe and not harmful to tissues. The insertion of SEDs into the plasma membrane is not toxic to cells; however, the intruding SEDs weaken the membrane's integrity. Under insonation, the ultrasound energy destabilized the SED disrupted membranes, resulting in membrane rupture and eventual cell death. In a xenograft breast tumor model, the SED alone or the ultrasound alone caused little adverse effects to tumor tissue, while the combined treatment triggered necrosis with a brief local insonation of 3 min. The described sonomembrane rupture therapy could be a safe alternative to the currently used high-energy tissue ablation technology, which uses X-rays, gamma rays, electron beams, protons, or high-intensity focused ultrasound.
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